Oncolytic peptides and uses thereof

Abstract

The present invention provides compositions for use in oncolytic peptide therapy of cancer. Methods of use of such compositions containing the oncolytic peptides are also described. In addition, the oncolytic peptide can be used for inhibiting tumor growth and reducing tumor volume.

Description

Technical Field

[0001] The present invention relates to an oncolytic peptide for inhibiting tumor growth and producing an anti-tumor response. Background Art

[0002] Cancer is one of the leading causes of morbidity and mortality, posing a global health burden as well as a heavy economic burden due to the costs associated with its monitoring and treatment.

[0003] Cancer cells are characterized by uncontrolled proliferation and the ability to invade surrounding normal tissues or distant sites by endocytic and / or lymphatic spread. The difficulty in effectively treating cancer involves establishing the distinction between malignant and normal cells in the body. Both originate from the same source and are very similar, so the immune system has no clear recognition of this threat.

[0004] Despite advances in cancer treatment over the past few decades, such as surgery, radiotherapy, chemotherapy, and immunotherapy, these treatment modalities are still associated with significant side effects. There is an unmet need for anticancer treatments with fewer side effects, and / or cancers that are resistant to chemotherapy or immunotherapy.

[0005] Therefore, the applicant has attempted to address the above-mentioned situations encountered in the prior art. Since peptide-based cancer therapeutics have the advantageous and inherent properties of being effective, safe and low-cost to produce, the present invention seeks to address several inherent deficiencies that need to be noted in the design and development of peptide-based cancer therapeutics. Summary of the invention

[0006] Cancer is the most common cause of death in developed countries. If cancer is diagnosed at an early stage, it is more likely to be successfully treated. Although considerable progress has been made in the diagnosis and treatment of cancer, these drugs either cause severe side effects or are ineffective. Therefore, a new method or new composition for treating cancer or preventing cancer is needed.

[0007] In order to solve the above problems, according to one embodiment of the present invention, a new method for treating cancer is provided, which is a constantly evolving process, and in this dynamic process, new active ingredients for treating cancer are developed.

[0008] Another aspect of the present invention provides a method of inhibiting or reducing cancer cells by administering a therapeutically effective amount of a peptide to a subject in need thereof.

[0009] In the following embodiments, the present invention is described in detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The drawings described herein are for illustration purposes only and are not intended to limit the scope of the present teachings in any way.

[0011] Figure 1A to Figure 1B is a schematic diagram of the B16-F10 melanoma experiment. Figure 1A In the experiment, SEQ ID NO: 9 was administered to the right flank of the mice, while the left flank of the mice was the untreated flank (only tumor). Figure 1B B16-F10 tumor cells were harvested, washed in culture medium, and injected intradermally (id) into the flanks of C57BL / 6 mice (3×10 per mouse). 6 B16-F10 cells / 50 μl RPMI-1640). Once a day for 5 consecutive days, the cells were injected into palpable tumors (20-30 mm 3 ) were injected (IT) with a single dose of SEQ ID NO: 9 dissolved in PBS (1.0 mg peptide / 50 μl PBS) and a blank control was saline (0.9% NaCl) only.

[0012] FIG. 2A to FIG. 2D It was shown that SEQ ID NO: 9 significantly inhibited tumor growth in vivo compared to the saline control group. The inhibitory effect was a systemic response and also inhibited the growth of distant tumors (left side) ( FIG. 2A to FIG. 2C In addition, SEQ ID NO: 9 prolonged the life span of tumor-bearing mice ( Figure 2D ). FIG. 2A to FIG. 2D The anti-tumor effect of SEQ ID NO: 9 in the B16-F10 tumor-bearing mouse model is shown. Representative images of B16F10 tumor-bearing mice on day 8 (before treatment) and day 12 after SEQ ID NO: 9 treatment or untreated group ( Figure 2A ). Changes in tumor size on the left or right side of the abdomen of B16-F10 tumor-bearing mice ( Figure 2B to Figure 2C ). Survival curve of SEQ ID NO:9 treated mice compared with untreated mice ( Figure 2D ).

[0013] FIG. 3A to FIG. 3B The results showed that the body weight and food intake were maintained after treatment with SEQ ID NO: 9 compared with the control group. The body weight of the control group (wild type), the untreated group (only B16-F10 tumor) and the SEQ ID NO: 9 treated group ( Figure 3A ). The food intake percentage of the control group (wild type), the untreated group (only B16-F10 tumor) and the SEQ ID NO:9 treated group ( Figure 3B ).

[0014] FIG. 4A to FIG. 4B This is a schematic diagram of the MN-11 fibrosarcoma experiment. Figure 4AIn the experiment, SEQ ID NO: 9 was administered to the right flank of the mice, while the left flank of the mice was the untreated flank (only tumor). Figure 4B MN-11 tumor cells were harvested, washed in culture medium, and injected subcutaneously (SC) into the flanks of C57BL / 6 mice (5×10 5 MN-11 cells / 50 μl RPMI-1640). Once a day for 5 consecutive days, the cells were injected into palpable tumors (100 mm 3 ) were injected (IT) with a single dose of SEQ ID NO: 9 dissolved in PBS (1.0 mg peptide / 50 μl PBS), and a blank control was saline (0.9% NaCl) only.

[0015] FIG. 5A to FIG. 5D The anti-tumor effect of SEQ ID NO: 9 in the MN-11 tumor-bearing mouse model is shown. Representative images of MN-11 tumor-bearing mice before treatment and after SEQ ID NO: 9 treatment or untreated groups ( Figure 5A ). Changes in tumor size on the left or right side of the abdomen of MN-11 tumor-bearing mice ( FIG. 5B to FIG. 5C ). Survival curve of SEQ ID NO:9 treated mice compared with untreated mice ( Figure 5D ).

[0016] FIG. 6A to FIG. 6B The results showed that SEQ ID NO:9 treatment maintained body weight and food intake compared to the saline control group. The body weight of the control group (wild type), untreated group (tumor only) and SEQ ID NO:9 treated group ( Fig. 6A ). The food intake percentage of the control group (wild type), the untreated group (tumor only) and the SEQ ID NO:9 treated group ( Figure 6B ).

[0017] FIG. 7A to FIG. 7B This is a schematic diagram of the EO771 breast cancer experiment. Fig. 7A In the experiment, SEQ ID NO: 9 was administered to the right flank of mice. Figure 7B EO771 tumor cells were harvested, washed in culture medium, and injected subcutaneously (sc) into the right flank of C57BL / 6 mice. (2×10 5 EO771 cells / 50 μl RPMI-1640). Once a day for 5 consecutive days, the cells were injected into palpable tumors (75 mm 3 ) were injected (IT intrathecally) with a single dose of SEQ ID NO: 9 dissolved in PBS (1.0 mg peptide / 50 μl PBS), and a blank control was saline (0.9% NaCl) only.

[0018] FIG. 8A to FIG. 8C The anti-tumor effect of SEQ ID NO: 9 in the EO771 tumor-bearing mouse model is shown. Representative images of EO771 tumor-bearing mice before treatment and after SEQ ID NO: 9 treatment or untreated groups ( Fig. 8A ). Changes in tumor size on the right side of the abdomen of EO771 tumor-bearing mice ( Figure 8B ). Survival curve of SEQ ID NO:9 treated mice compared with untreated mice ( Figure 8C ).

[0019] FIG. 9A to FIG. 9B The results showed that the body weight and food intake were maintained after treatment with SEQ ID NO: 9 compared with the control group. The body weight of the control group (wild type), the untreated group (EO771 tumor only) and the SEQ ID NO: 9 treated group ( Fig. 9A ). The food intake percentage of the control group (wild type), the untreated group (EO771 tumor only) and the SEQ ID NO:9 treated group ( Fig. 9B ). DETAILED DESCRIPTION

[0020] Although preferred embodiments of the present invention are shown and described herein, such embodiments are provided by way of example only and are not intended to limit the scope of the present invention in other ways. Various alternatives to the embodiments described herein may be employed in implementing the present invention.

[0021] Unless otherwise defined, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0022] The terms "amino acid sequence", "protein", "polypeptide" and "peptide" are used interchangeably herein to refer to two or more amino acids or "residues" covalently linked by an amide bond or equivalent. The amino acid sequence may be linked by non-natural or non-amide chemical bonds.

[0023] In one embodiment, the oncolytic peptide has the general formula (I): X m -(AC 1 X) n -(DLC 2 )X q , wherein X is selected from the group consisting of basic amino acids; wherein A is selected from the group consisting of aromatic amino acids; wherein C1 or C2 is selected from the group consisting of basic amino acids or non-polar amino acids; wherein D is selected from the group consisting of aromatic amino acids or unnatural amino acids; wherein L is leucine; and m of the general formula (I) is 4 to 8, q is 0 to 2, and n is 0 to 2.

[0024] In another embodiment, the basic amino acid is selected from the group consisting of lysine, arginine and histidine.

[0025] In another embodiment, the aromatic amino acid is selected from the group consisting of tryptophan, phenylalanine and tyrosine.

[0026] In another embodiment, the non-polar amino acid is selected from the group consisting of leucine, alanine, valine, isoleucine, proline, phenylalanine, methionine and tryptophan.

[0027] In another embodiment, the unnatural amino acid is selected from the group consisting of β-naphthylalanine (Nal), (benzothiophen-3-yl)alanine (Bal), diphenylalanine (Dip), (4,4'-diphenyl-yl)alanine (Bip), (anthracen-9-yl)alanine (Ath), and (2,5,7-tri-tert-butyl-indol-3-yl)alanine (Tht).

[0028] In another embodiment, the C-terminus of the oncolytic peptide is formed in part by a modification group consisting of amidation, acetylation, formylation, hydroxylation, lipid modification, methylation, and phosphorylation.

[0029] The present invention also provides a pharmaceutical composition for treating cancer or inhibiting tumor growth, comprising a therapeutically effective amount of the oncolytic peptide of the present invention and a pharmaceutically acceptable excipient.

[0030] In one embodiment, the cancer comprises melanoma, fibrosarcoma, prostate cancer, breast cancer, uterine cancer, leukemia, ovarian cancer, endometrial cancer, cervical cancer, colorectal cancer, testicular cancer, lymphoma, rhabdomyosarcoma, neuroblastoma, pancreatic cancer, lung cancer, brain tumor, skin cancer, stomach cancer, oral cancer, liver cancer, laryngeal cancer, gallbladder cancer, thyroid cancer, liver cancer, kidney cancer or nasopharyngeal cancer.

[0031] As used herein, the term "therapeutically effective amount" means the amount of an oncolytic peptide that effectively produces a desired therapeutic response in a specific patient (subject) suffering from cancer. In particular, the term "therapeutically effective amount" includes the amount of a therapeutic agent that will achieve the desired therapeutic effect when administered. In the context of the present invention, the therapeutic effect thereof includes partial or complete inhibition, delay or prevention of cancer progression (including cancer metastasis), inhibition, delay or prevention of cancer recurrence (including cancer metastasis) and / or prevention of cancer from occurring or developing in the subject. Regarding the therapeutic amount of a therapeutic agent (i.e., an oncolytic peptide), it is also considered that the amount of each therapeutic agent used to treat the subject should be sufficiently low within the scope of reasonable medical judgment to avoid adverse or serious side effects. When used in combination, the therapeutically effective amount will vary due to the age and physical condition of the end user, the severity of the cancer, the duration of treatment, the nature of any other concurrent treatment, the specific type of therapeutic agent used for treatment, the pharmaceutically acceptable specific carrier used in the pharmaceutical composition containing the therapeutic agent, and other relevant factors.

[0032] As used herein, "subject" is generally a human subject, and includes, but is not limited to, a cancer patient. The subject can be male or female, and can be of any race or ethnicity. The subject can be of any age, including a newborn, infant, toddler, child, adolescent adult, or elderly. The subject can also include an animal subject, particularly a mammalian subject, such as a canine, feline, bovine, caprine, equine, ovine, porcine, rodent (e.g., mouse, rat, guinea pig, and hamster), lagomorph, primate (including non-human primates), etc.

[0033] The dosage of the oncolytic peptide of the present invention is appropriately determined according to the purpose of treatment and conditions such as sex, age, body weight of the test subject, administration route and disease severity.

[0034] The terms "administration" and "administering" include the introduction of the oncolytic peptides of the present invention into a subject to perform their intended functions. The oncolytic peptides of the present invention can be administered orally, buccally, parenterally, via spray inhalation, rectally, intradermally, transdermally or topically in a unit dosage formulation containing conventional non-toxic and pharmaceutically acceptable carriers, adjuvants and excipients as needed.

[0035] As used herein, "treating" or "treatment" refers to the treatment or therapy of a disease or medical condition (such as cancer, tumor, tumor disorder) of a subject (such as a mammal, especially a human being), which includes: improving the disease or medical condition, that is, eliminating the disease or medical condition of the subject / patient or causing its regression; inhibiting the disease or medical condition, that is, slowing down or stopping the progression of the disease or medical condition of the subject / patient; or alleviating the symptoms of the disease or medical condition of the subject / patient.

[0036] As used herein, the term "pharmaceutically acceptable" means that the carrier, diluent, excipient and / or salt used in the composition should be compatible with the other ingredients of the formulation and not harmful to the recipient thereof. "Pharmaceutically acceptable" also means that the composition or dosage form is suitable for use in subjects such as animals or humans within the scope of reasonable medical judgment, at a reasonable benefit / risk ratio, without excessive toxicity, irritation, allergic reaction or other problems or complications.

[0037] The oncolytic peptides of the present invention can be administered in a single dose, in multiple doses over a 24-hour period, or by continuous infusion. When administered by continuous infusion, the drug can be provided by methods known in the art, such as, but not limited to, intravenous gravity drip, intravenous infusion pump, implantable infusion pump, etc., or any local route. The duration of treatment will depend on many factors. Treatment of a subject with the oncolytic peptides of the present invention alone or in combination with other agents can continue throughout the subject's life.

[0038] Other specific embodiments of the present invention include but are not limited to the following.

[0039] Example

[0040] The embodiments encompassed herein are now described with reference to the following examples. These examples are provided for illustrative purposes only, and the disclosure encompassed herein should not be construed in any way as being limited to these examples, but rather should be construed to include any and all variations that become apparent as a result of the teachings provided herein.

[0041] The data of the following examples were analyzed using GraphPad Prism version. All results of the following examples are expressed as mean ± SD of at least two independent experimental results. The results were analyzed using one-way ANOVA and Student's t-test. P values ​​< 0.05 were considered statistically significant.

[0042] Example 1

[0043] Oncolytic peptides

[0044] In an exemplary embodiment of the present invention, the oncolytic peptide of the present invention may optionally include, but is not limited to, SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10.

[0045] The sequences of SEQ ID NO: 1 to SEQ ID NO: 10 that can be used according to the present invention are shown in Table 1 below.

[0046] Table 1 Oncolytic peptide sequences

[0047]

[0048] Example 2

[0049] Half-inhibitory concentration of oncolytic peptides for cytotoxicity assay of cancer cell lines

[0050] The MTT assay is a colorimetric method for measuring the activity of enzymes in living cells, reducing thiazolyl blue tetrazolium bromide (MTT) to formazan crystals and producing a purple color. In this example, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazodiumbromide (MTT) activity colorimetric assay was used to evaluate the in vitro cytotoxicity of oncolytic peptides.

[0051] The half inhibitory concentration (IC50) is the concentration of an oncolytic peptide required to achieve 50% inhibition. In one embodiment, IC50 testing is performed using an oncolytic peptide using the MTT colorimetric assay.

[0052] In this embodiment, human lung cancer cell lines PC9 and A549 and mouse pancreatic cancer cell line Panc02 were cultured in RPMI medium supplemented with 10% fetal bovine serum and antibiotics. On the other hand, mouse liver cancer cell line Hepa 1-6, mouse melanoma cell line B16-F10, mouse fibrosarcoma cell line MN-11, mouse breast cancer cell line EO771 and human diploid fibroblast (HFW) were cultured in DMEM medium supplemented with 10% fetal bovine serum and antibiotics. Cell culture was performed in a humidified incubator at 37°C with 5% CO2.

[0053] All cancer cell lines were seeded in 96-well plates at a concentration of 5000-8000 cells / 100 μl per well and cultured for 24 hours. After removing the medium, 100 μl of fresh medium containing peptides (ranging from 50 μM-0.8 μM) was added to the wells. After 24 hours of culture, the medium was replaced with fresh medium containing MTT (0.5 mg / ml) and cultured for 3 hours. After removing the medium / MTT, 100 μl of DMSO was added to dissolve the formazan crystals. TM The absorbance at 540 nm was measured using a TECAN multi-labeled microplate reader, and the cell survival rate was calculated.

[0054] The data showed that the oncolytic peptides had potent anticancer activity against different cancer cell lines (Table 2).

[0055] Table 2. Oncolytic peptides administered at half inhibitory concentrations to cancer cell lines.

[0056]

[0057]

[0058] As disclosed in Table 2, the anticancer ability is ranked as follows: SEQ ID NO: 7-9> SEQ ID NO: 1-3≈SEQ ID NO: 4-6> SEQ ID NO: 10. Compared with the data of half-inhibitory concentration, this reveals that the combination of "KKKKRR", "WRKWLKWLA" and "β-naphthylalanine (Nal)" in the oncolytic peptide will have better anticancer activity. In addition, the length of the peptide sequence connected after "KKKKRR" is a key factor in anticancer activity.

[0059] Example 3

[0060] Peptide stability in serum

[0061] Due to the high toxicity of this type of peptide, the inventors hope that the peptide can be decomposed after inducing cancer cells to release danger-associated molecular patterns (DAMPs) and will not stay in the body for too long. After exposure to 25% (vol / vol) fetal bovine serum, the residues of the peptides were analyzed by liquid chromatography, and the stability at different time points was calculated. The results showed that the peptide of SEQ ID NO: 7 decreased by nearly 40% at the 4th hour and 44% remained after 8 hours, indicating that the peptide decomposed after interacting with tumor cells and would not accumulate in the human body (Table 3).

[0062] Table 3 Serum stability results of SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:9.

[0063] Time (hours) 0 0.5 1 2 4 6 8 SEQ ID NO:7 100.00％ 100.80％ 123.30％ 72.10％ 59.50％ 54.40％ 44.40％ SEQ ID NO:8 100.00％ 104.90％ 77.40％ 106.20％ 70.40％ 71.30％ 66.50％ SEQ ID NO:9 100.00％ 90.70％ 76.20％ 77.90％ 70.90％ 74.20％ 55.80％

[0064] The serum stability of oncolytic peptides at 4 hours was ranked as follows: SEQ ID NO: 9> SEQ ID NO: 8> SEQ ID NO: 7. There was no positive correlation between the number of amino acid residues of oncolytic peptides and serum stability. However, serum stability was positively correlated with β-naphthylalanine (Nal) in the peptide sequence. In addition, the serum stability of oncolytic peptides at 6 hours was ranked as follows: SEQ ID NO: 9> SEQ ID NO: 8> SEQ ID NO: 7. However, the stability of oncolytic peptides in serum for 8 hours was ranked as follows: SEQ ID NO: 8> SEQ ID NO: 9> SEQ ID NO: 7.

[0065] Example 4

[0066] Animal experiments

[0067] C57BL / 6 female mice (4-6 weeks old) purchased from BioLASCO Taiwan Co., Ltd. were used as allogeneic model animals and were kept in a controlled environment without specific pathogens. During the experiment, female mice weighed 180-240g each, with 4-6 animals per cage as a group, and were raised under controlled climate conditions with a 12-hour light / dark cycle and a suitable temperature. Mice were kept in enriched individual ventilated cages (Half inhibitory concentrations of the oncolyticpeptides tested with cancerous cell lines, IVC) systems with free access to standard rodent food and water. During the experiment, animals were anesthetized with 2.5% isoflurane gas. Animals were monitored every day. All procedures were carried out in accordance with the regulations and animal protection laws set up and managed by the Laboratory Animal Care and Use Committee or group.

[0068] Once a day for 5 consecutive days, inject the 50 μg / ml thiazide solution into the palpable tumor (e.g., 20-30 mm in B16-F10 tumor-bearing mice). 3 , 100 mm for MN-11 tumor-bearing mice 3 , 75 mm for EO771 tumor-bearing mice 3 ) A single dose injection (IT intrathecal injection) of SEQ ID NO: 9 (1.0 mg peptide / 50 μl PBS) and a blank control of saline only (0.9% NaCl).

[0069] Tumor size was measured 3 times per week using calipers, and tumor volume was calculated using the following formula: tumor size (mm 3 )=0.5×(width 2 × length). The results are shown as volume ± SEM. The survival rate of tumor-bearing mice was continuously observed and recorded until all animals died.

[0070] Example 5

[0071] Inhibits melanoma growth and prolongs survival in an allograft animal model

[0072] To evaluate the in vivo effects of SEQ ID NO:9, this example used the B16-F10 allogeneic model in C57BL / 6 mice ( Figure 1A to Figure 1B B16-F10 tumor cells were harvested, washed in culture medium, and injected intradermally (id) into the flanks of C57BL / 6 mice (3×10 per mouse). 6 B16-F10 cells / 50 μl RPMI-1640).

[0073] This example demonstrates that SEQ ID NO: 9 significantly inhibited tumor growth in vivo compared to the saline control group, and that the inhibitory effect was a systemic response that also inhibited the growth of distal tumors (left side) ( FIG. 2A to FIG. 2D In addition, treatment with SEQ ID NO: 9 did not cause significant changes in body weight or food intake in mice, suggesting that SEQ ID NO: 9 may not have toxic effects in vivo ( FIG. 3A to FIG. 3B ). The reason for weight loss after treatment is presumed to be due to excessive swelling of the tumor.

[0074] Example 6

[0075] Inhibits fibrosarcoma growth and prolongs survival in allogeneic transplant animal models

[0076] To evaluate the in vivo effects of SEQ ID NO:9, this example used the MN-11 allogeneic model in C57BL / 6 mice ( FIG. 4A to FIG. 4B MN-11 tumor cells were obtained, washed in culture medium, and injected subcutaneously (SC) into the flanks of C57BL / 6 mice (5×10 5 MN-11 cells / 50 μl RPMI-1640).

[0077] This embodiment demonstrates that SEQ ID NO: 9 significantly inhibited the growth of unilateral (right) tumors in vivo compared with the saline control group (Figure) ( FIG. 5A to FIG. 5DIn addition, during the treatment with SEQ ID NO: 9, the body weight and food intake of mice did not change significantly, which means that SEQ ID NO: 9 does not have toxic effects in vivo. The reason for the weight loss after treatment is presumably caused by excessive tumor swelling ( FIG. 6A to FIG. 6B ).

[0078] Example 7

[0079] Inhibits breast cancer and prolongs survival in an allograft mouse model

[0080] To evaluate the in vivo effects of SEQ ID NO:9, this example used the EO771 allogeneic model in C57BL / 6 mice ( FIG. 7A to FIG. 7B EO771 tumor cells were harvested, washed in culture medium, and injected subcutaneously (sc) into the right flank of C57BL / 6 mice (2×10 5 EO771 cells / 50 μl RPMI-1640).

[0081] This example demonstrates that SEQ ID NO:9 significantly inhibited tumor growth in vivo compared to a saline control group ( FIG. 8A to FIG. 8C In addition, during the treatment with SEQ ID NO: 9, the body weight and food intake of mice did not change significantly, which means that SEQ ID NO: 9 has no toxic effects in vivo ( FIG. 9A to FIG. 9B ).

[0082] In summary, in the present invention, SEQ ID NO: 9 prolongs the life span of tumor-bearing mice ( Figure 2D , Figure 5D and Figure 9C). These results indicate that SEQ ID NO:9 can significantly inhibit tumor growth and improve the survival rate of C57BL / 6 tumor-bearing mice.

[0083] The above is an explanation of the present invention, but it should not be understood as limiting the present invention. The present invention is defined by the following claims, including equivalents of the claims.

Claims

1. An oncolytic peptide, the general formula (I) is: X m -(AC1X) n -(DLC2)X q , in, X is selected from the group consisting of basic amino acids; wherein A is selected from the group consisting of aromatic amino acids; wherein C1 or C2 is selected from the group consisting of basic amino acids or non-polar acids; wherein D is selected from the group consisting of aromatic amino acids or unnatural amino acids; and Wherein, L is leucine.

2. The oncolytic peptide according to claim 1, wherein The basic amino acid is selected from the group consisting of lysine, arginine and histidine.

3. The oncolytic peptide according to claim 2, wherein m is 4 to 8.

4. The oncolytic peptide according to claim 2, wherein q is 0 to 2.

5. The oncolytic peptide according to claim 2, wherein n is 0 to 2.

6. The oncolytic peptide according to claim 5, wherein The aromatic amino acid is selected from the group consisting of tryptophan, phenylalanine and tyrosine.

7. The oncolytic peptide according to claim 5, wherein The non-polar acid is selected from the group consisting of leucine, alanine, valine, isoleucine, proline, phenylalanine, methionine and tryptophan.

8. The oncolytic peptide according to claim 5, wherein The unnatural amino acid is selected from the group consisting of β-naphthylalanine (Nal), (benzothiophen-3-yl)alanine (Bal), diphenylalanine (Dip), (4,4'-diphenyl-yl)alanine (Bip), (anthracen-9-yl)alanine (Ath) and (2,5,7-tri-tert-butyl-indol-3-yl)alanine (Tht).

9. The oncolytic peptide according to claim 8, wherein The C-terminus of the oncolytic peptide is formed in part by a modification group consisting of amidation, acetylation, formylation, hydroxylation, lipid modification, methylation, and phosphorylation.

10. The oncolytic peptide according to claim 9, wherein The oncolytic peptide is selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO:

10.

11. A method of using an oncolytic peptide comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1 to 10 to a subject in need thereof.

12. The method of using an oncolytic peptide according to claim 11, wherein: The subject is diagnosed with cancer.

13. The method of using an oncolytic peptide according to claim 12, wherein: The cancer includes melanoma, fibrosarcoma, prostate cancer, breast cancer, uterine cancer, leukemia, ovarian cancer, endometrial cancer, cervical cancer, colorectal cancer, testicular cancer, lymphoma, rhabdomyosarcoma, neuroblastoma, pancreatic cancer, lung cancer, brain tumor, skin cancer, stomach cancer, oral cancer, liver cancer, laryngeal cancer, gallbladder cancer, thyroid cancer, liver cancer, kidney cancer or nasopharyngeal cancer.

14. The method of using an oncolytic peptide according to claim 11, wherein: The subject is selected from mammals.

15. The method of using an oncolytic peptide according to claim 14, wherein: The mammal is selected from the group consisting of cats, dogs, rabbits, cows, horses, sheep, goats, monkeys, mice, rats, gerbils, guinea pigs, pigs and humans.

16. The use of the oncolytic peptide according to claim 1, wherein: The oncolytic peptide is administered to a subject in need thereof in a therapeutically effective amount.

17. The use of the oncolytic peptide according to claim 16, wherein: The subject is diagnosed with cancer.

18. The use of the oncolytic peptide according to claim 17, wherein: The cancer includes melanoma, fibrosarcoma, prostate cancer, breast cancer, uterine cancer, leukemia, ovarian cancer, endometrial cancer, cervical cancer, colorectal cancer, testicular cancer, lymphoma, rhabdomyosarcoma, neuroblastoma, pancreatic cancer, lung cancer, brain tumor, skin cancer, stomach cancer, oral cancer, liver cancer, laryngeal cancer, gallbladder cancer, thyroid cancer, liver cancer, kidney cancer or nasopharyngeal cancer.

19. The use of the oncolytic peptide according to claim 18, wherein: The subject is selected from mammals.

20. The use of an oncolytic peptide according to claim 19, wherein: The mammal is selected from the group consisting of cats, dogs, rabbits, cows, horses, sheep, goats, monkeys, mice, rats, gerbils, guinea pigs, pigs and humans.

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